Phosphatase Subfamily DSP10
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP10 (MKP5)
DSP10 selectively dephosphorylates p38 and JNK. It is conserved across holozoan but lost in nematodes.
Evolution
DSP10 (MKP5) subfamily is found in most holozoan except nematodes. DSP10 is usually one copy per genome, e.g. DUSP10 in human.
Domain
DSP10 has two domains: rhodanese domain and phosphatase domain. Rhodanese domain can bind to kinases [1].
Function
DUSP10 is phosphatase specific for p38 and SAPK/JNK. It binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate. It is present evenly in both the cytoplasm and the nucleus. DUSP10 is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli [2, 3, 4].
On the other hand, it has been reported that DUSP10 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription [5].
Human DUSP10 is frequently upregulated in colorectal cancer (CRC). Certain mutations in DUSP10 correlate with the incidence of CRC. DUSP10/MKP5 also negatively regulates intestinal epithelial cell growth [6].
References
- Tao X and Tong L. Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5. Protein Sci. 2007 May;16(5):880-6. DOI:10.1110/ps.062712807 |
- Tanoue T, Moriguchi T, and Nishida E. Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5. J Biol Chem. 1999 Jul 9;274(28):19949-56. DOI:10.1074/jbc.274.28.19949 |
- Theodosiou A, Smith A, Gillieron C, Arkinstall S, and Ashworth A. MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases. Oncogene. 1999 Nov 25;18(50):6981-8. DOI:10.1038/sj.onc.1203185 |
- Jeong DG, Yoon TS, Kim JH, Shim MY, Jung SK, Son JH, Ryu SE, and Kim SJ. Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase. J Mol Biol. 2006 Jul 28;360(5):946-55. DOI:10.1016/j.jmb.2006.05.059 |
- Nomura M, Shiiba K, Katagiri C, Kasugai I, Masuda K, Sato I, Sato M, Kakugawa Y, Nomura E, Hayashi K, Nakamura Y, Nagata T, Otsuka T, Katakura R, Yamashita Y, Sato M, Tanuma N, and Shima H. Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas. Oncol Rep. 2012 Sep;28(3):931-6. DOI:10.3892/or.2012.1862 |
- Png CW, Weerasooriya M, Guo J, James SJ, Poh HM, Osato M, Flavell RA, Dong C, Yang H, and Zhang Y. DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis. Oncogene. 2016 Jan 14;35(2):206-17. DOI:10.1038/onc.2015.74 |
